TLR2/4 promotes PGE2 production to increase tissue damage in Escherichia coli-infected bovine endometrial explants via MyD88/p38 MAPK pathway

Tingting Li; Lili Hai; Bo Liu; Wei Mao; Kun Liu; Yuan Shen; Qianru Li; Yuli Guo; Yan Jia; Haixia Bao; Jinshan Cao

doi:10.1016/j.theriogenology.2020.04.004

TLR2/4 promotes PGE₂ production to increase tissue damage in Escherichia coli-infected bovine endometrial explants via MyD88/p38 MAPK pathway

Theriogenology. 2020 Aug:152:129-138. doi: 10.1016/j.theriogenology.2020.04.004. Epub 2020 Apr 7.

Authors

Tingting Li¹, Lili Hai², Bo Liu², Wei Mao², Kun Liu², Yuan Shen², Qianru Li², Yuli Guo², Yan Jia², Haixia Bao², Jinshan Cao³

Affiliations

¹ College of Veterinary Medicine, China Agricultural University, Beijing, China; Key Laboratory of Clinical Diagnosis and Treatment Techniques of Animal Disease for Ministry of Agriculture, College of Veterinary Medicine, Inner Mongolia Agricultural University, Huhhot, China.
² Key Laboratory of Clinical Diagnosis and Treatment Techniques of Animal Disease for Ministry of Agriculture, College of Veterinary Medicine, Inner Mongolia Agricultural University, Huhhot, China.
³ Key Laboratory of Clinical Diagnosis and Treatment Techniques of Animal Disease for Ministry of Agriculture, College of Veterinary Medicine, Inner Mongolia Agricultural University, Huhhot, China. Electronic address: [email protected].

PMID: 32408026
DOI: 10.1016/j.theriogenology.2020.04.004

Abstract

Prostaglandin E2 (PGE₂), a lipid mediator, is released by several cell types including endometrial cells and plays a central role in bacterial infection of the endometrium during inflammation. PGE₂ production accumulated in Escherichia coli (E. coli) -infected bovine endometrial tissue, which increased E. coli-infected endometrial tissue damage. However, the mechanisms of PGE₂ accumulation in the E. coli-infected endometrium during inflammation-associated endometrial tissue damage remain unclear. This study was conducted to investigate the role of Toll-like receptors (TLRs) 2 and 4 in increased PGE₂ production in E. coli-infected endometrial tissue. E. coli and TLR2/4 agonists significantly induced cyclooxygenase-2 and microsomal prostaglandin E synthase-1 expression and PGE₂ synthesis detected by RT-PCR, Western blot, and ELISA in the endometrial tissue. The expression and synthesis were dramatically decreased by TLR4, myeloid differentiation factor88 (MyD88), and p38 mitogen-activated protein kinase (MAPK) inhibitors in E. coli-infected endometrial tissue. These inhibitors also significantly decreased proinflammatory factor (interleukin-6 and tumor necrosis factor-α) and damage-associated molecular pattern (high mobility group box-1 and hyaluronan-binding protein-1) release and tissue damage measured by double-label immunofluorescence in E. coli-infected endometrial explants. Our work provides in vitro evidence that TLR2/4-MyD88/p38 MAPK promotes PGE₂ synthesis and E. coli-infected endometrial tissue damage, which may be useful for improving PGE₂-based therapies for endometritis.

Keywords: Escherichia coli infection; Inflammatory damage; Prostaglandin E2 accumulation; Toll-like receptor-MyD88/p38 mitogen-activated protein kinase pathway.

MeSH terms

Animals
Cattle
Dinoprostone / genetics
Dinoprostone / metabolism
Endometrium / microbiology*
Escherichia coli / classification
Escherichia coli / metabolism*
Female
Gene Expression
Gene Expression Regulation / drug effects
Heterocyclic Compounds, 2-Ring / administration & dosage
Heterocyclic Compounds, 2-Ring / pharmacology
Imidazoles / administration & dosage
Imidazoles / pharmacology
Lactones / administration & dosage
Lactones / pharmacology
Lipopeptides / administration & dosage
Lipopeptides / pharmacology
Lipopolysaccharides / administration & dosage
Lipopolysaccharides / pharmacology
Myeloid Differentiation Factor 88 / antagonists & inhibitors
Myeloid Differentiation Factor 88 / genetics
Myeloid Differentiation Factor 88 / metabolism*
Pyridines / administration & dosage
Pyridines / pharmacology
Sesquiterpenes / administration & dosage
Sesquiterpenes / pharmacology
Spiro Compounds / administration & dosage
Spiro Compounds / pharmacology
Sulfonamides / administration & dosage
Sulfonamides / pharmacology
Tissue Culture Techniques
Toll-Like Receptor 2 / agonists
Toll-Like Receptor 2 / antagonists & inhibitors
Toll-Like Receptor 2 / metabolism*
Toll-Like Receptor 4 / agonists
Toll-Like Receptor 4 / antagonists & inhibitors
Toll-Like Receptor 4 / metabolism*
p38 Mitogen-Activated Protein Kinases / antagonists & inhibitors
p38 Mitogen-Activated Protein Kinases / genetics
p38 Mitogen-Activated Protein Kinases / metabolism*

Substances

Heterocyclic Compounds, 2-Ring
Imidazoles
Lactones
Lipopeptides
Lipopolysaccharides
Myeloid Differentiation Factor 88
Pam(3)CSK(4) peptide
Pyridines
ST2825
Sesquiterpenes
Spiro Compounds
Sulfonamides
Toll-Like Receptor 2
Toll-Like Receptor 4
atractylenolide I
ethyl 6-(N-(2-chloro-4-fluorophenyl)sulfamoyl)cyclohex-1-ene-1-carboxylate
p38 Mitogen-Activated Protein Kinases
Dinoprostone
4-(4-fluorophenyl)-2-(4-hydroxyphenyl)-5-(4-pyridyl)imidazole